We have found that hypoxia causes dilation as well as constriction of the pulmonary vasculature. Preliminary studies indicated that adenosine, released by lung tissue during hypoxia, may be responsible for this vasodilation. We will test this possibility in isolated lungs by determining if the enzyme adenosine deaminase, which inactivates adenosine, inhibits hypoxic pulmonary vasodilation. Inasmuch as enzymes characteristically exhibit a high degree of substrate specificity, a positive result will constitute strong evidence in favor of this hypothesis. In addition, we will determine the effects of adenosine antagonists, which should also block the vasodilation, and inhibitors of adenosine cellular uptake and native adenosine deaminase, which should accentuate it. Finally, lung tissue levels of adenosine will be correlated with PO2 over a wide range of O2 tensions. To determine if hypoxic pulmonary vasodilation is an inherent property of pulmonary vascular smooth muscle, we will measure the relationships between O2 tension on the one hand and isometric tension and transmembrane potential on the other in isolated pulmonary vessels. To assess the physiologic significance of hypoxic pulmonary vasodilation, we will determine if it occurs in intact animals and what effects it has on ventilation-perfusion matching in the lung. These studies should further elucidate the effects of hypoxia on pulmonary vessels and the mechanism of those effects.